Galloylated Toll-Like Receptor 7/8 Agonist Nanovaccine for Enhanced Tumor Antigen Delivery in Personalized Immunotherapy

Abstract

Cancer vaccines, a critical technology in cancer immunotherapy, have shown great therapeutic potential. However, traditional vaccines based on tumor cell lysates (TCLs) have shown disappointing results in early clinical trials due to low immunogenicity, in vivo instability, and the inability to codeliver with adjuvants. To address these issues, we developed a nanoparticle vaccine, R848-GA@TCLs, by modifying the toll-like receptor 7/8 (TLR7/8) agonist R848 with gallic acid. This nanovaccine leverages the “capturing” ability of the galloyl moiety to coload TCLs and R848, forming stable nanoparticles. R848-GA@TCLs efficiently target lymph nodes, increasing TCL accumulation 10-fold, and enable the synchronized release of antigens and adjuvants within dendritic cells (DCs). Our results show that R848-GA@TCLs increase with respect to the cross-presentation of tumor antigens, promote the production of pro-inflammatory cytokines, and activate DCs, leading to a significant increase in effector T cells, natural killer (NK) cells, and M1 macrophages. This strong immune response resulted in potent antitumor effects, with R848-GA@TCLs demonstrating efficacy in multiple tumor models by significantly inhibiting tumor growth and metastasis. In conclusion, R848-GA@TCLs represent a personalized cancer vaccine capable of codelivering TCLs and adjuvants, eliciting robust antitumor immune responses, and hold great potential for clinical applications.